DOCSLIB.ORG

Enabling FIB-SEM Systems for Large Volume Connectomics and Cell Biology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Enabling FIB-SEM Systems for Large Volume Connectomics and Cell Biology bioRxiv preprint doi: https://doi.org/10.1101/852863; this version posted November 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Enabling FIB-SEM Systems for Large Volume Connectomics and Cell Biology C. Shan Xu*, Song Pang, Kenneth J. Hayworth, and Harald F. Hess Janelia Research Campus, Howard Hughes Medical Institute 19700 Helix Dr., Ashburn, VA 20147, USA Abstract Isotropic high-resolution imaging of large volumes provides unprecedented opportunities to advance connectomics and cell biology research. Conventional Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) offers unique benefits such as high resolution (< 10 nm in x, y, and z), robust image alignment, and minimal artifacts for superior tracing of neurites. However, its prevailing deficiencies in imaging speed and duration cap the maximum possible image volume. We have developed technologies to overcome these limitations, thereby expanding the image volume of FIB-SEM by more than four orders of magnitude from 103 µm3 to 3 x 107 µm3 while maintaining an isotropic resolution of 8 x 8 x 8 nm3 voxels. These expanded volumes are now large enough to support connectomic studies, in which the superior z resolution enables automated tracing of fine neurites and reduces the time-consuming human proofreading effort. Moreover, by trading off imaging speed, the system can readily be operated at even higher resolutions achieving voxel sizes of 4 x 4 x 4 nm3, thereby generating ground truth of the smallest organelles for machine learning in connectomics and providing important insights into cell biology. Primarily limited by time, the maximum volume can be greatly extended. Here we provide a detailed description of the enhanced FIB-SEM technology, which has transformed the conventional FIB-SEM from a laboratory tool that is unreliable for more than a few days to a robust imaging platform with long term reliability: capable of years of continuous imaging without defects in the final image stack. An in-depth description of the systematic * Correspondence to: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/852863; this version posted November 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. approach to optimize operating parameters based on resolution requirements and electron dose boundary conditions is also explicitly disclosed. We further explore how this technology unleashes the full potential of FIB-SEM systems, revolutionizing volume electron microscopy (EM) imaging for biology by gaining access to large sample volumes with single-digit nanoscale isotropic resolution. Key words FIB-SEM, Volume Electron Microscopy, 3D imaging, Large Volume, 3D Structure, Isotropic Resolution, Connectomics, Cell Biology, Drosophila, Mouse, Mammalian Cell Introduction Connectomics aims to decipher the functions of brains by mapping their neural circuits. The findings will not only guide the next generation of development in deep learning and artificial intelligence but will also transform our understanding of the brain, in both healthy and diseased states. It can enhance research to find cures for brain disorders and perhaps even pave the way to ultimately comprehend the human mind. Connectomics extracts the connectivity of neurons in the brain as a basis for understanding its function. The brain features that must be imaged with high resolution vary greatly in size, from the nm scale of the synapse to the mm length scale of the neurons that form even the smallest circuits. In three dimensions, these dimensional scales, taken to the third power, translate to 3D image stacks that can easily reach 10,0003 or Tera voxels. Furthermore, the data must maintain a high degree of accuracy and continuity, because even a few missing image planes could compromise the ability to reconstruct a neuron and trace its contribution to a neuronal network, invalidating months of data acquisition. These technical requirements have shaped the adaptation and development of FIB-SEM as a 3D volume imaging technique. The enhanced FIB-SEM technology developed at Howard Hughes Medical Institute’s Janelia Research Campus (1) has overcome the limitations of conventional volume electron microscopy methods, emerging as a novel approach for connectomic research. FIB-SEM has been described previously in detail. It is a technique that has been used in materials science and the semiconductor industry for multiple decades. It has more recently bioRxiv preprint doi: https://doi.org/10.1101/852863; this version posted November 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. been applied in biological imaging since 2006 (2). FIB-SEM uses scanning electron microscopy to raster scan the surface of a planar sample with a fine electron beam, a few nanometers in diameter, and monitors that surface by the back scattered electrons along with secondary electrons. Biological tissues are typically stained with heavy metals, such as osmium, which binds preferentially to the cell membranes and lipids thus enhancing the electron scattering signal at such locations. After imaging, the focused Ion beam (FIB), typically comprising 30 keV gallium ions, strafes across the imaged surface and ablates a few nanometers from the top of the sample to expose a new slightly deeper surface for subsequent imaging. Cycles of etching and imaging gradually erode away the sample while enabling the collection of a stack of consecutive 2D images, usually requiring tens of seconds to a few minutes per cycle. Compared with serial thin section imaging (3, 4, 5), block-face based approaches (1, 2, 6, 7) provide greater consistency and stability of the image, thereby resulting in much better self- aligned image stacks. This is particularly important for connectomic studies: a well-registered and defect-free image stack is the foundation for successful automated segmentation. Serial sections incorporate folds and other imperfections in the sections thus posing significant challenges in registration and segmentation. Both diamond knife and FIB are options for the precise removal of material necessary for block-face based 3D imaging. FIB-based removal, unlike diamond knife, removes tissue at the atomic level without any mechanical moving components. It therefore offers the potential for nanometer control of the z-axis resolution. FIB milling is also less sensitive to damage by electron radiation from the SEM beam, so it can tolerate a higher electron dose to provide better signal-to-noise ratio (SNR) imaging (details of which are discussed in sections on Standard Resolution Mode and High Throughput Mode). The major disadvantages of conventional FIB-SEM include the slow imaging acquisition rate and lack of long-term stability. Additionally, the process of material ablation depletes the FIB gallium source in three to four days, so that just a few tens of microns in z thickness can be imaged before a pause is required to replenish the gallium source. After a pause, imprecise beam position could then result in excessive material loss while re-engaging the beam. Other factors such as room temperature fluctuations can disturb the fine control of the increment in z axis milling. These limitations constrain conventional FIB-SEM to small volumes. bioRxiv preprint doi: https://doi.org/10.1101/852863; this version posted November 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. To meet the large volume demands of connectomics, a number of enhancements to conventional FIB-SEM are discussed below. These enhancements have dramatically improved long-term reliability, and hence enabled uniform defect-free z increments that can support imaging of hundreds of microns in sample thickness. This represents a new regime in sample size and resolution for 3D volume imaging, with minimal trade-off between large volume and fine resolution. To probe biological questions with the most appropriate technology, it is necessary to characterize various platforms through a unified metric—minimum isotropic resolution, defined by the worst case in the x, y, or z axis. Because each imaging technology yields different resolutions in three axes, inferior resolution in any dimension can limit useful resolution in the other two, and impair the quality of subsequent image processing and analysis. Figure 1 provides an overview of the volume EM operating space. Specifically, it highlights the sample volume and minimum isotropic resolution that can be accessed only by long-term FIB-SEM imaging, and compares this to that by other volume EM imaging modalities. For example, diamond-knife cut serial section TEM with tomography, e.g. using ~500-nm-thick sections, can give better spatial resolution at the cost of imaging volume, shown at the lower left of Figure 1. Conversely, even larger volumes with lower spatial resolution can be collected by diamond-knife cut serial section TEM or diamond-knife cut serial block-face SEM (SBFSEM), both enclosed for reference at the top of Figure 1. The space at the lower right of Figure 1 invites a technology for connectomic studies: the fine neurites can be traced at any random orientations without degradation of resolution, while neurons expanded over long distance can be fully captured by the large volume. Our enhanced FIB-SEM system delivers a larger volume with fine spatial resolution, addressing the need for connectomic studies. The red diagonal dotted lines indicate contours of constant imaging time: For a given time allotted for data acquisition, one may choose either finer resolution at the expense of sample volume or vice- versa. To explore this FIB-SEM application space, we break the regime into three domains, labeled simply: high resolution, standard resolution, and high throughput (reduced resolution).
Load more

Recommended publications
  • New Trends in Connectomics
    FOCUS FEATURE: New Trends in Connectomics Editorial: New Trends in Connectomics 1 2,3,4,5 Olaf Sporns and Danielle S. Bassett 1Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA 2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA 3Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA, USA 4Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 5Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, USA ABSTRACT Connectomics is an integral part of network neuroscience. The field has undergone rapid Downloaded from http://direct.mit.edu/netn/article-pdf/02/02/125/1092204/netn_e_00052.pdf by guest on 28 September 2021 expansion over recent years and increasingly involves a blend of experimental and computational approaches to brain connectivity. This Focus Feature on “New Trends in an open access journal Connectomics” aims to track the progress of the field and its many applications across different neurobiological systems and species. The idea that connections among neural elements are crucial for brain function has been central to modern neuroscience almost since its inception. Building on this idea, the emerg- ing field of connectomics adds several new and important components. First, connectomics provides comprehensive maps of neural connections, with the ultimate goal of achieving com- plete coverage of any given nervous system. Second, connectomics delivers insights into the principles that underlie network architecture and uncovers how these principles support net- work function. These dual aims can be accomplished through the confluence of new experi- mental techniques for mapping connections and new network science methods for modeling and analyzing the resulting large connectivity datasets.
    [Show full text]
  • Connectomics of Morphogenetically Engineered Neurons As a Predictor of Functional Integration in the Ischemic Brain
    http://www.diva-portal.org This is the published version of a paper published in Frontiers in Neurology. Citation for the original published paper (version of record): Sandvig, A., Sandvig, I. (2019) Connectomics of Morphogenetically Engineered Neurons as a Predictor of Functional Integration in the Ischemic Brain Frontiers in Neurology, 10: 630 https://doi.org/10.3389/fneur.2019.00630 Access to the published version may require subscription. N.B. When citing this work, cite the original published paper. Permanent link to this version: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-161446 REVIEW published: 12 June 2019 doi: 10.3389/fneur.2019.00630 Connectomics of Morphogenetically Engineered Neurons as a Predictor of Functional Integration in the Ischemic Brain Axel Sandvig 1,2,3 and Ioanna Sandvig 1* 1 Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway, 2 Department of Neurology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway, 3 Department of Pharmacology and Clinical Neurosciences, Division of Neuro, Head, and Neck, Umeå University Hospital, Umeå, Sweden Recent advances in cell reprogramming technologies enable the in vitro generation of theoretically unlimited numbers of cells, including cells of neural lineage and specific neuronal subtypes from human, including patient-specific, somatic cells. Similarly, as demonstrated in recent animal studies, by applying morphogenetic neuroengineering principles in situ, it is possible to reprogram resident brain cells to the desired phenotype. These developments open new exciting possibilities for cell replacement therapy in Edited by: stroke, albeit not without caveats.
    [Show full text]
  • Patient-Tailored Connectomics Visualization for the Assessment of White Matter Atrophy in Traumatic Brain Injury
    Patient-Tailored Connectomics Visualization for the Assessment of White Matter Atrophy in Traumatic Brain Injury The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Irimia, Andrei, Micah C. Chambers, Carinna M. Torgerson, Maria Filippou, David A. Hovda, Jeffry R. Alger, Guido Gerig, et al. 2012. Patient-tailored connectomics visualization for the assessment of white matter atrophy in traumatic brain injury. Frontiers in Neurology 3:10. Published Version doi://10.3389/fneur.2012.00010 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:8462352 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA METHODS ARTICLE published: 06 February 2012 doi: 10.3389/fneur.2012.00010 Patient-tailored connectomics visualization for the assessment of white matter atrophy in traumatic brain injury Andrei Irimia1, Micah C. Chambers 1, Carinna M.Torgerson1, Maria Filippou 2, David A. Hovda2, Jeffry R. Alger 3, Guido Gerig 4, Arthur W.Toga1, Paul M. Vespa2, Ron Kikinis 5 and John D. Van Horn1* 1 Laboratory of Neuro Imaging, Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA 2 Brain Injury Research Center, Departments of Neurology and Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA 3 Department of Radiology, David
    [Show full text]
  • Brain Connectivity Meets Reservoir Computing
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.22.427750; this version posted January 23, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Brain Connectivity meets Reservoir Computing Fabrizio Damicelli1, Claus C. Hilgetag1, 2, Alexandros Goulas1 1 Institute of Computational Neuroscience, University Medical Center Hamburg Eppendorf, Hamburg University, Hamburg, Germany 2 Department of Health Sciences, Boston University, Boston, MA, USA * [email protected] Abstract The connectivity of Artificial Neural Networks (ANNs) is different from the one observed in Biological Neural Networks (BNNs). Can the wiring of actual brains help improve ANNs architectures? Can we learn from ANNs about what network features support computation in the brain when solving a task? ANNs’ architectures are carefully engineered and have crucial importance in many recent perfor- mance improvements. On the other hand, BNNs’ exhibit complex emergent connectivity patterns. At the individual level, BNNs connectivity results from brain development and plasticity processes, while at the species level, adaptive reconfigurations during evolution also play a major role shaping connectivity. Ubiquitous features of brain connectivity have been identified in recent years, but their role in the brain’s ability to perform concrete computations remains poorly understood. Computational neuroscience studies reveal the influence of specific brain connectivity features only on abstract dynamical properties, although the implications of real brain networks topologies on machine learning or cognitive tasks have been barely explored. Here we present a cross-species study with a hybrid approach integrating real brain connectomes and Bio-Echo State Networks, which we use to solve concrete memory tasks, allowing us to probe the potential computational implications of real brain connectivity patterns on task solving.
    [Show full text]
  • A Multi-Pass Approach to Large-Scale Connectomics
    A Multi-Pass Approach to Large-Scale Connectomics Yaron Meirovitch1;∗;z Alexander Matveev1;∗ Hayk Saribekyan1 David Budden1 David Rolnick1 Gergely Odor1 Seymour Knowles-Barley2 Thouis Raymond Jones2 Hanspeter Pfister2 Jeff William Lichtman3 Nir Shavit1 1Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology 2School of Engineering and Applied Sciences, 3Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University ∗These authors equally contributed to this work zTo whom correspondence should be addressed: [email protected] Abstract The field of connectomics faces unprecedented “big data” challenges. To recon- struct neuronal connectivity, automated pixel-level segmentation is required for petabytes of streaming electron microscopy data. Existing algorithms provide relatively good accuracy but are unacceptably slow, and would require years to extract connectivity graphs from even a single cubic millimeter of neural tissue. Here we present a viable real-time solution, a multi-pass pipeline optimized for shared-memory multicore systems, capable of processing data at near the terabyte- per-hour pace of multi-beam electron microscopes. The pipeline makes an initial fast-pass over the data, and then makes a second slow-pass to iteratively correct errors in the output of the fast-pass. We demonstrate the accuracy of a sparse slow-pass reconstruction algorithm and suggest new methods for detecting mor- phological errors. Our fast-pass approach provided many algorithmic challenges, including the design and implementation of novel shallow convolutional neural nets and the parallelization of watershed and object-merging techniques. We use it to reconstruct, from image stack to skeletons, the full dataset of Kasthuri et al.
    [Show full text]
  • A Critical Look at Connectomics
    EDITORIAL A critical look at connectomics There is a public perception that connectomics will translate directly into insights for disease. It is essential that scientists and funding institutions avoid misrepresentation and accurately communicate the scope of their work. onnectomes are generating interest and excitement, both among ­nervous ­system, dubbed the classic connectome because it is ­currently neuroscientists and the public. This September, the first grants the only wiring diagram for an animal’s entire nervous system at the level Cunder the Human Connectome Project, totaling $40 ­million of the synapse. Although major neurobiological insights have been made over 5 years, were awarded by the US National Institutes of Health using C. elegans and its known connectivity and genome, there are still (NIH). In the public arena, striking, colorful pictures of human brains many questions remaining that can only be answered by hypothesis-driven have ­accompanied claims that imply that understanding the complete experiments. For example, we still don’t completely understand the process ­connectivity of the human brain’s billions of neurons by a trillion ­synapses of axon regeneration, relevant to spinal cord injury in humans, in this is not only ­possible, but that this will also directly translate into insights comparatively simple system. Thus, a connectome, at any resolution, is for neurological and psychiatric disorders. Even a press release from only one of several complementary tools necessary to understand nervous the NIH touted that the Human Connectome Project would map the system disease and injury. ­wiring diagram of the entire living human brain and would link these There are substantial efforts aimed at generating connectomes for circuits to the full spectrum of brain function in health and disease.
    [Show full text]
  • Connectomics and Molecular Imaging in Neurodegeneration
    European Journal of Nuclear Medicine and Molecular Imaging (2019) 46:2819–2830 https://doi.org/10.1007/s00259-019-04394-5 REVIEW ARTICLE Connectomics and molecular imaging in neurodegeneration Gérard N. Bischof1,2 & Michael Ewers3 & Nicolai Franzmeier3 & Michel J. Grothe4 & Merle Hoenig1,5 & Ece Kocagoncu 6 & Julia Neitzel3 & James B Rowe6,7 & Antonio Strafella8,9,10,11,12 & Alexander Drzezga1,5,13 & Thilo van Eimeren1,13,14 & on behalf of the MINC faculty Received: 29 May 2019 /Accepted: 4 June 2019 / Published online: 11 July 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Our understanding on human neurodegenerative disease was previously limited to clinical data and inferences about the underlying pathology based on histopathological examination. Animal models and in vitro experiments have provided evidence for a cell-autonomous and a non-cell-autonomous mechanism for the accumulation of neuropathology. Combining modern neuroimaging tools to identify distinct neural networks (connectomics) with target-specific positron emission tomography (PET) tracers is an emerging and vibrant field of research with the potential to examine the contributions of cell-autonomous and non-cell-autonomous mechanisms to the spread of pathology. The evidence pro- vided here suggests that both cell-autonomous and non-cell-autonomous processes relate to the observed in vivo char- acteristics of protein pathology and neurodegeneration across the disease spectrum. We propose a synergistic model of cell-autonomous and non-cell-autonomous accounts that integrates the most critical factors (i.e., protein strain, suscep- tible cell feature and connectome) contributing to the development of neuronal dysfunction and in turn produces the observed clinical phenotypes.
    [Show full text]
  • Adam H. Marblestone Adam.H.Marblestone [At] Gmail [Dot] Com
    Adam H. Marblestone www.adammarblestone.org Adam.H.Marblestone [at] gmail [dot] com Experience Google DeepMind Research Scientist, Oct 2018- Neuroscience-inspired artificial intelligence. Kernel Chief Strategy Officer, Jan 2017-August 2018 Technologies for interfacing with the human brain. [$53M from leading VCs, 2020] MIT Media Lab Research Scientist and “Director of Scientific Architecting”, Synthetic Neurobiology Group, 2014-2017. Research affiliate, 2017-2020 Advisor: Ed Boyden Inventing methods for scalable and comprehensive brain circuit analysis, in-situ RNA sequencing, protein sequencing, 3D nanofabrication, and neural recording. BioBright LLC Co-founder, 2012-2020 [Acquired by Dotmatics, 2020] “Smart Lab” startup funded by investments, DARPA, and industry contracts. Dana Farber Cancer Institute Intern, 2007 Advisors: William Shih, Shawn Douglas Research on DNA nanotechnology. [Co-authored leading design software for the field, cited over 700 times in the scientific literature.] Education Harvard University Ph.D., Biophysics, 2014 Thesis: Designing scalable biological interfaces Advisor: George Church Research on bio-nanotechnology, synthetic biology and molecular tickertapes. Technology roadmaps for scalable neural recording and connectomics. Yale University B.S., Physics, 2009 Advisor: Michel Devoret Research on quantum information theory and superconducting quantum circuits. Key Publications (* indicates equal contribution) [H-Index: 15, Citations: >2500] Physical principles for scalable neural recording Adam H. Marblestone*, Brad Zamft*, Yael Maguire, Mikhail Shapiro, Josh Glaser, Ted Cybulski, Dario Amodei, P. Benjamin Stranges, Reza Kalhor, David Dalrymple, Dongjin Seo, Elad Alon, Michel M. Maharbiz, Jose M. Carmena, Jan M. Rabaey, Ed Boyden**, George Church**, Konrad Kording** Frontiers in Computational Neuroscience (2013). Featured in Nature Physics. Towards an integration of deep learning and neuroscience Adam H.
    [Show full text]
  • Promisomics and the Short-Circuiting of Mind
    Commentary | Cognition and Behavior Promisomics and the Short-Circuiting of Mind https://doi.org/10.1523/ENEURO.0521-20.2021 Cite as: eNeuro 2021; 10.1523/ENEURO.0521-20.2021 Received: 2 December 2020 Revised: 3 January 2021 Accepted: 11 January 2021 This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data. Alerts: Sign up at www.eneuro.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Copyright © 2021 Gomez-Marin This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. 1 Promisomics and the short-circuiting of mind 2 Alex Gomez-Marin 3 Instituto de Neurociencias de Alicante, SPAIN 4 [email protected] 5 6 (January 6th, 2021) 7 8 9 Significance Statement: Grand neuroscience projects, such as connectomics, have a recurrent 10 tendency to overpromise and underdeliver. Here I critically assess what is done in contrast with 11 what is claimed about such endeavors, especially when the results are "horizontal" and the 12 conclusions "vertical", namely, when maps of one level (synaptic connections) are conflated with 13 mappings between levels (neural function, animal behavior, cognitive processes). I argue that to 14 suggest that connectomics will give us the mind of a mouse, a human or even a fly is 15 theoretically flawed at many levels.
    [Show full text]
  • A Neuromechanical Model and Kinematic Analyses for Drosophila Larval Crawling Based on Physical Measurements
    bioRxiv preprint doi: https://doi.org/10.1101/2020.07.17.208611; this version posted July 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 A neuromechanical model and kinematic analyses for Drosophila 2 larval crawling based on physical measurements 3 4 Xiyang Suna, Yingtao Liub, Chang Liuc, Koichi Mayumic, Kohzo Itoc, Akinao 5 Nosea,b, Hiroshi Kohsakaa,* 6 7 a Department of Complexity Science and Engineering, Graduate School of 8 Frontier Science, the University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, 277- 9 8561 Chiba, Japan 10 b Department of Physics, Graduate School of Science, the University of Tokyo, 7- 11 3-1 Hongo, Bunkyo-ku, 133-0033 Tokyo, Japan 12 c Department of Advanced Materials Science, Graduate School of Frontier 13 Science, the University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, 277-8561 Chiba, 14 Japan 15 * For correspondence: ([email protected], +81-04-7136-3922) 16 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.17.208611; this version posted July 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 17 Abstract 18 Animal locomotion requires dynamic interactions between neural circuits, muscles, and 19 surrounding environments. In contrast to intensive studies on neural circuits, the 20 neuromechanical basis for animal behaviour remains unclear due to the lack of information 21 on the physical properties of animals.
    [Show full text]
  • USING BRAIN CONNECTOMICS to DETECT FUNCTIONAL CONNECTIVITY DIFFERENCES in ALZHEIMER's DISEASE Joey Annette Contreras Submitted
    USING BRAIN CONNECTOMICS TO DETECT FUNCTIONAL CONNECTIVITY DIFFERENCES IN ALZHEIMER’S DISEASE Joey Annette Contreras SubmitteD to the Faculty oF the University GraDuate School in partial FulFillment oF the requirements For the Degree Doctor oF Philosophy in the Program oF MeDical Neuroscience, InDiana University October 2017 AccepteD by the GraDuate Faculty oF InDiana University, in partial FulFillment oF the requirements For the Degree oF Doctor oF Philosophy. Doctoral Committee ___________________________________ Karmen K YoDer PhD, Chair ___________________________ AnDrew J Saykin PsyD _____________________ Joaquín Goñi Cortes PhD July 10, 2017 _______________________ OlaF Sporns PhD ______________________ Mario DzemiDzic PhD ______________________ Li Shen PhD ii DEDICATION This thesis is DeDicateD, First anD Foremost, to my parents, Joe anD Rosario Contreras, anD my brother, Jacob Contreras, For the constant support anD For instilling me with the courage to achieve my goals not only through their verbal anD emotional encouragement, but through their actions as well. SpeciFically, my DaD, an MTA bus Driver For over 35 years, has shown me the importance oF a strong work ethic and responsibility to Family, how to be compassionate to others you Don’t know, anD what it is to have the spirit oF the bear;) My mother, a secretary turneD CEO oF her own company, has taught me that liFe will always surprise you anD Failure is something to never shy away From, but rather an opportunity to better yourselF anD grow. She taught me to be stubborn but ask For help, anD she taught me that, in the enD, I want to grow up to be just as beautiFully anD unapologetically intelligent as she is.
    [Show full text]
  • Connecting a Connectome to Behavior: an Ensemble of Neuroanatomical Models of C. Elegans Klinotaxis
    Connecting a Connectome to Behavior: An Ensemble of Neuroanatomical Models of C. elegans Klinotaxis Eduardo J. Izquierdo*, Randall D. Beer Cognitive Science Program, Indiana University, Bloomington, Indiana, United States of America Abstract Increased efforts in the assembly and analysis of connectome data are providing new insights into the principles underlying the connectivity of neural circuits. However, despite these considerable advances in connectomics, neuroanatomical data must be integrated with neurophysiological and behavioral data in order to obtain a complete picture of neural function. Due to its nearly complete wiring diagram and large behavioral repertoire, the nematode worm Caenorhaditis elegans is an ideal organism in which to explore in detail this link between neural connectivity and behavior. In this paper, we develop a neuroanatomically-grounded model of salt klinotaxis, a form of chemotaxis in which changes in orientation are directed towards the source through gradual continual adjustments. We identify a minimal klinotaxis circuit by systematically searching the C. elegans connectome for pathways linking chemosensory neurons to neck motor neurons, and prune the resulting network based on both experimental considerations and several simplifying assumptions. We then use an evolutionary algorithm to find possible values for the unknown electrophsyiological parameters in the network such that the behavioral performance of the entire model is optimized to match that of the animal. Multiple runs of the evolutionary algorithm produce an ensemble of such models. We analyze in some detail the mechanisms by which one of the best evolved circuits operates and characterize the similarities and differences between this mechanism and other solutions in the ensemble. Finally, we propose a series of experiments to determine which of these alternatives the worm may be using.
    [Show full text]